Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma.

OBJECTIVE: To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). METHODS AND MATERIALS: From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ''In-Field (IF)'', "Marginal recurrence" or ''Out-of-Field (OF)'' if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. RESULTS: We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6-28.9 cc), while the mean MTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61-91%) and 4 recurrences were marginal to MTVpre (1-33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). CONCLUSION: Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.

Depression and cardiovascular risk-association among Beck Depression Inventory, PCSK9 levels and insulin resistance.

BACKGROUND: Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. RESULTS: In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. CONCLUSIONS: This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

Diabetes and work: The need of a close collaboration between diabetologist and occupational physician.

AIM: The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. DATA SYNTHESIS: Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. CONCLUSIONS: Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Urinary chromium is associated with changes in leukocyte miRNA expression in obese subjects.

BACKGROUND/OBJECTIVES: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs. SUBJECTS/METHODS: We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software. RESULTS: Urinary Cr levels (mean: 0.35 µg/l; s.d.=0.24) ranged from 0.05 to 1.27 µg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (ß=-0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (ß=2.1; P=0.004) and systolic BP (ß=3.3; P=0.003). CONCLUSIONS: These results indicate that miR-451 and miR-486-3p are involved in the link between Cr levels and metabolic diseases and CVDs.

Correlation between salivary and serum oxidized LDL levels: a pilot study on overweight/obese subjects.

BACKGROUND: Saliva contains a variety of substances and could be functionally equivalent to serum in reflecting the physiological state of the body, including metabolic variations. Salivary samples are non-invasive, safe, and easier to handle than serum. Oxidized LDL cholesterol (oxLDL) is an additional cardiovascular risk factor playing an important role in atheromatous plaque formation; overweight/obese subjects present an increase in oxLDL concentrations. The aims of the study were to assess oxLDL salivary levels, if detectable, and to verify their possible correlation with serum in overweight/obese subjects. METHODS: Thirty-five consecutive overweight/obese subjects and 10 normal weight controls were enrolled. Serum and salivary oxLDL levels were measured by a commercial enzyme-linked-immunosorbent assay (ELISA method). RESULTS: oxLDL levels were detectable in salivary samples and correlated (P = 0.001) with serum levels. Overweight/obese subjects showed serum and salivary oxLDL levels higher than controls (P = 0.000 and P = 0.022, respectively). CONCLUSIONS: Our study showed the presence of oxLDL in salivary samples and highlighted a correlation between salivary oxLDL levels and their counterpart in serum. Moreover, salivary oxLDL levels were higher in overweight/obese subjects than in controls. Therefore, a salivary sample could be functionally equivalent to serum in monitoring cardiovascular risk in overweight/obese subjects.

Permeability of gloves used in nuclear medicine departments to [(99m)Tc]-pertechnetate and [(18)F]-fluorodeoxyglucose: radiation protection considerations.

In order to evaluate the safety of the individual protection devices, the permeability of four different types of disposable gloves, commonly used in hospitals, was tested in relation to [(99m)Tc]-pertechnetate and to [(18)F]-fluorodeoxyglucose ([(18)F]-FDG). From these radiopharmaceutical solutions, a drop was deposited on the external surface of the glove which was opened and stretched with the external surface placed upward. The smear test technique permitted to evaluate the activity onto the inner surface of the glove at different times. The smear tests were measured in a well sodium iodide detector calibrated in efficiency for (99m)Tc and (18)F. The permeability was tested on ten samples of each type of gloves and was expressed as the ratio of the activity onto the inner surface at each time interval to the activity deposited on the external surface of the glove. For each type of gloves and for each sampling time, mean value, standard deviation and percentage coefficient of variation of permeability were evaluated. One type of gloves showed a low resistance to permeation of both radiopharmaceuticals, while another one only to pertechnetate. The other gloves were good performers. The results of this study suggest to test permeability for gloves used for handling radiopharmaceuticals, before their adoption in the clinical routine. This practice will provide a more careful service of radiation protection for nuclear medicine department staff.

[Prevalence of obstructive sleep apnea syndrome in a group of obese workers]. / La prevalenza della sindrome delle apnee ostruttive del sonno un gruppo di lavoratori affetti da obesità.

The Obstructive Sleep Apnea Syndrome (OSAS) is a quite diffused in workers disease, mainly in obese or overweight subjects. This syndrome can cause cardiovascular and cerebral complications and have negative effects on job performances. We evaluated 214 obese/overweight workers referred from different job areas. A diagnosis of OSAS was pre-existent in about 5% of the examined subjects, and clinical elements suggesting suspect of OSAS were present in about 15% of the sample. The risk of development Obstructive Sleep Apnea Syndrome seems to be linear correlated with BMI, neck and waist circumference. We did not find any correlation between OSAS risk and job area. We strongly suggest that health surveillance should include the evaluation of the possible presence of sleep disorders to reduce the risks associated and the negative consequences on job performances.

[Workplace campaigns for metabolic syndrome prevention and healthy lifestyles promotion in mechanical engineering industries]. / Interventi per la prevenzione della sindrome metabolica e la promozione di stili di vita salutari in aziende del settore metalmeccanico.

The paper describes 2 years outcome on BMI, smoking habits and physical activity of 2 WHP carried in engineering plants. Three important results were achieved: stationarity of body weight despite ageing of examined population; increase of workers that perform regular physical activity and a slight increase of smoking cessation. NSAS questionnaire showed a marked improvement in life styles compared to the data obtained 2 years before. Our findings suggest that an efficacy on life style modification can be achieved by WHP campaigns with little time and cost consuming. The collaboration between occupational physician, employer and employees but also with external professionals is the key of success.

[Applicability of the test SIO on obesity-related disability (TSD-OC) in occupational medicine for the evaluation of work problems linked to overweight-obesity condition]. / Applicabilità del Test SIO sulla disabilità correlata all'obesità (TSD-OC) in Medicina del Lavoro per la valutazione di problematiche lavorative legate al sovrappeso-obesità.

Obesity is frequently associated with functional changes that may affect work capacity, so we administered to a group of 198 overweight-obese subjects with median BMI of 32.7 and median waist circumference of 101 cm, the test-TSD OC which consists of 7 sections (pain, stiffness, activities of daily life, activities of the house, instrumental activities of daily living, work, social relations) for a total of 36 visual analogical scales. After the identification of 4 workers categories (health, services, administration, commerce/industry), resulted homogeneous for age, BMI, CV, we saw that the work section was more compromised for health and services. The overall disability increases especially in relation to BMI and seems influenced by age and sex.

[Comparison of indexes for assessing insulin resistance for the health surveillance among workers]. / Confronto tra indici per la valutazione dell'insulinoresistenza nella sorveglianza sanitaria dei lavoratori.

Night shift workers present a high risk to develop metabolic and cardiovascular disorders for alterations that involve effects on circadian rhythms at the level of insulin resistance (IR). Monitor such parameter in this category of workers, therefore, is a crucial step in health surveillance. To this aim, the currently in use test consists in the calculation of the HOMA index [basal insulin (MU/ml) x basal glycemy(mmol/l)/22.5], a measurement with a considerable cost (about 13 Euros). Recent studies demonstrated that the measurement of TyG index calculated as Ln[Triglycerids (mg/dl) x Glucose(mg/dl)/2] and of the triglycerids/HDL-cholesterol ratio correlates with HOMA index. These analyses cost altogether about 5 Euros, allowing a clear decrease of expenses. Our study, carried out on 217 workers at Centre for Obesity and Occupational Medicine of the Occupational Medicine Clinic of Milan, confirmed such correlation and identified the TyG as the index with the best cost/performance ratio. Our future goal is to establish cut-off values, necessary to adopt the TyG as first choice index.

Five-year experience of quality control for a 3D LSO-based whole-body PET scanner: results and considerations.

PET scanners require routine monitoring and quality control (QC) to ensure proper scanner performance. QC helps to ensure that PET equipment performs as specified by the manufacturer and that there have not been significant changes in the system response since acceptance. In this work we describe the maintenance history and we report on the results obtained from the PET system QC testing program over 5 years at two centers, both utilizing a Siemens Biograph 16 HiRez PET/CT system. QC testing programs were based on international standards and included the manufacturer's daily QC, monthly uniformity and sensitivity, quarterly cross-calibration and annual resolution and image quality. For the Winnipeg and Novara sites, two and one PET detector blocks have been replaced, respectively. Neither system has had other significant PET system related hardware replacements. The manufacturer's suggested daily QC was sensitive to detecting problems in the function of PET detector elements. The same test was not sensitive for detecting long term drifts in the systems: the Novara system observed a significant deterioration over five years of testing in the sensitivity which exhibited a decrease of 16% as compared to its initial value measured at system installation. The measure of the energy spectrum, showed that the 511 keV photopeak had shifted to a position of 468 keV. This shift was corrected by having service personnel perform a complete system calibration and detector block setup. We recommend including tests of system energy response and of sensitivity as part of a QC program since they can provide useful information on the actual performance of the scanner. A modification of the daily QC test by the manufacturer is suggested to monitor the long term stability of the system. Image quality and spatial resolution tests have proven to be of limited value for monitoring the system over time.

[Vitamin D as a cardiovascular risk factor in workers]. / La vitamina D come fattore di rischio cardiovascolare nei lavoratori.

Numerous evidence suggests that vitamin D deficiency is implicated in the development of cardiovascular risk. It has been investigated the relationship between cardiovascular risk factors and vitamin D concentrations in 264 consecutive workers from Centro Obesità e Lavoro della Clinica del Lavoro di Milano. For these studies, glicometaboliche analysis, anthropometric measurements and impedance evalutation were performed and questionnaires to estimate nutrient levels in the diet were administered. The levels of vitamin D are found to be deficient in 166 patients (less than 20 ng/mL), insufficient in 63 patients (less than 30 ng/mL) and optimal for the remaining 35 patients. A significant negative association was observed between the concentrations of vitamin D and cardiovascular risk factors (HOMA ratio and TG/HDL) ratios and BMI. Vitamin D is a cardiovascular risk factor "corrected" for example by changing the eating habits of workers.

[Evaluation of the work-related disability in people affected by Ehlers-Danlos syndrome]. / Valutazione della disabilità in ambito lavorativo in soggetti con sindrome di Ehlers-Danlos.

The Ehlers-Danlos syndrome (EDS), inherited disorder of connective tissue, frequently leads to impairment of various functional areas, including employment. In 35 subjects with classic type EDS, 14 hypermobile, 3 vascular was administered 7 visual analogical scales (pain, stiffness, activities of daily living, instrumental activities of daily living, work, social relations). An impairment of particular significance in total score and in individual areas emerges is in the hypermobile group, followed by classic, less for the vasculature. Overall there is a significant alteration of the quality of life that deserves proper evaluation to facilitate the definition of fitness and the improvement of job insertion in patients with EDS.

Improving palliative treatment of patients with non-operable cancer of the oesophagus: training doctors and nurses in the use of self-expanding metal stents (SEMS) in Malawi.

Cancer of the oesophagus is the 6th most common cancer in Malawi. Nationwide only three hospitals are able to perform oesophagectomies, and there is no radiotherapy or chemotherapy available. Owing to late presentation of the patients (sometimes in combination with co-morbidities such as HIV/AIDS or tuberculosis) the vast majority of patients are not suitable for surgery. Self-expanding metal stents (SEMS) of the oesophagus provide a suitable palliative option to improve the quality of life for patients. This project took a nationwide approach, raising funds for both technical equipment and training of endoscopists and nursing staff throughout Malawi.

Characterization of the [(153)Sm]Sm-EDTMP pharmacokinetics and estimation of radiation absorbed dose on an individual basis.

[(153)Sm]Sm-EDTMP is a radiopharmaceutical used in palliation cares of bone metastases. The purpose of this study is to provide an explicit description of [(153)Sm]Sm-EDTMP pharmacokinetics, adopting a simple three-compartmental model with the analytical expressions calculating the rate constants and determining biodistribution parameters, like radiopharmaceutical uptake and clearance. This biokinetic model allowed us to calculate on an individual basis the dose to bone surface and to red bone marrow and to assess the degree of variability in dosimetric parameters using a fixed administered activity based only on patient weight. In this study twenty patients were enrolled and were treated with [(153)Sm]Sm-EDTMP, administering a fixed activity per kilogram (37 MBq/kg); blood and urine samples were collected during 24 h post treatment. The median value of the administered activity was 2.7 GBq. Blood clearance confirmed that an aliquot of [(153)Sm]Sm-EDTMP rapidly localizes and is retained in bone, while the remainder is rapidly cleared from the blood pool by the urinary system. Our data show a bi-exponential clearance from blood: the rapid component has a half life median value of 6 min (range: 2-24 min), while the slow one has a half life median value of 1.4 h (range: 0.6-5.8 h). Median value of the urinary excretion is 40 (range: 3-75) % of the administered activity. Our model shows the behaviour of a tracer which is distributed in the extracellular space of the body, localized in the skeleton and excreted via glomerular filtration. Half life median values of [(153)Sm]Sm-EDTMP transferring between compartments, T(1/2) (blood→ECF), T(1/2) (ECF→blood) are 7.4 (range: 1.9-37) and 48 (range: 8-408) min, respectively. Median values of half lives of [(153)Sm]Sm-EDTMP clearance through the urine and of uptake into bone are 1.0 (range: 0.1-6.0) and 1.6 (range: 0.6-9.0) h, respectively. Median value of red marrow absorbed dose is 2.1 (range: 0.7-3.5) Gy and 0.8 (range: 0.3-2.1) Gy/GBq, while median value of bone surface absorbed dose is 11.5 Gy (range: 5.0-18.4) and 4.4 (range: 2.3-14.3) Gy/GBq. It is remarkable that there is a really great biological variability within patients, especially considering the excreted activity. The cumulated activity in bone and red marrow doses were significantly higher in prostate cancer, where metastatic bone lesions are osteoblastic, than in breast cancer where metastatic bone lesions are osteolytic or mixed (lytic/blastic). The relevant biological variability in biodistribution and metabolism of [(153)Sm]Sm-EDTMP suggests that the fixed administered activity based on patient weight is not sufficient to optimize the treatment and a better optimization would be reached by using a predictive dosimetry tailored to individual patient characteristics.

[Impact of obesity-related disability in different work categories]. / Impatto dello disabilità correlata all'obesità nelle diverse categorie professionali.

Absenteeism and sick leave are often reported in obese workers. To evaluate disability work related we assess 180 overweight-obese subjects [BMI 34,6 + 6,4, range 26,0-59,0) with TSD-OC questionnaire divided into 7 items (pain; stiffness; ADL; housework; IADL; occupational activities; social life) with a total of 36 visual analogue scales. Among the job categories, health-care workers showed the highest TSD-OC total score (26,9 + 22,5%, ANOVA p < 0,05) and BMI (BMI 37,7 + 6,9 kg/m2). Among the items, pain was statistically significant in health-care workers (16,1 + 13,2%), in Services (16,3 + 14,3%), in Education (15,1 + 11,4%) and in Administration (13,3 +11,0%) ( p <0,05). "Occupational activities" item was statistically significant in health-care (11, 6 +10,6%, p <0,05).

["EOSS" classification in a group of obese workers]. / Classificazione "EOSS" in un gruppo di lavoratori obesi.

Current classification of obesity, based on BMI, presents some limitations in evaluating work-related impairments. In fact it does not provide information on presence and/or severity of clinical impairments associated with obesity. On the contrary, EOSS classification takes into account metabolic complications and functional limitations with restrictions of daily living and working activities. Aim of our study is to compare, in a group of obese workers, the different utility for precautionary and work-eligibility purposes of these two classifications. Results on our study population suggest that a more systematic use of the EOSS classification might be useful in occupational medicine.

Use of total reflection X-ray fluorescence (TXRF) for the evaluation of heavy metal poisoning due to the improper use of a traditional ayurvedic drug.

An Indian patient referred to Clinica del Lavoro 'L.Devoto' of Milano showed clinical signs of heavy metal poisoning, possibly related to a sustained 6-month use of approx. 3 g/day of a traditional preparation (a whitish powder with a 'mineral' appearance) to treat urological problems. To confirm the causal relationship between the disease and the use of such product, metal testing was performed on the patient's hair and the ayurvedic remedy samples by total reflection X-ray fluorescence (TXRF). For TXRF analysis 1-cm cut of the patient's hair was directly deposited onto the quartz glass sample carrier, then 10 microl of nitric acid 65% were added and dried in air. TXRF showed high versatility, rapid and simultaneous element detection, and short analysis time, thus supporting a wider use in emergency medicine and in forensic analyses.

[Disseminated tuberculosis with cutaneous manifestations in AIDS patients. Presentation of 4 cases]. / Tuberculosis diseminada con manifestaciones cutáneas en pacientes con SIDA. A propósito de 4 observaciones.

BACKGROUND: Acute cutaneous miliary tuberculosis is a rare form of Mycobacterium tuberculosis infection which has been described in only 25 published cases in the last 15 years. The appearance of serious disseminated forms of tuberculosis is enhanced by the severe immunodeficiency which characterizes AIDS. METHODS: Four cases are described of disseminated tuberculosis with cutaneous localization clinically described as the acute miliary form. Patients had AIDS and CD4 lymphocyte levels of < 100 cells/mm3. Diagnosis was established in all cases by scraping of cutaneous lesions and direct examination with Ziehl-Neelsen coloration. RESULTS: The 4 patients presented signs and symptoms of disseminated tuberculosis with cutaneous manifestations, without a definite pattern and with localization predominantly on the thorax. Three had BAAR-positive sputum. Multiresistant strains of Mycobacterium tuberculosis were confirmed by antibiogram. One patient infected by a strain sensitive to first-line drugs responded favorably to conventional treatment for disseminated tuberculosis. In the remaining three with multiresistant strains, the evolution of the disease was rapid and unfavorable. CONCLUSIONS: Abrupt appearance of cutaneous lesions in a patient with disseminated tuberculosis and advanced HIV-disease should raise the suspicion of its etiology. Scraping and direct examination using Ziehl-Neelsen coloration is practical, economical and non-invasive diagnostic method.